After balloon angioplasty, a metal tubular scaffold structure called a stent may be permanently implanted to physically hold open the repaired coronary artery. Unfortunately, up to 30% of such procedures result in reclosure (restenosis) of the artery within six months to one year. One solution to the problem is to provide acute local, postoperative radiation treatment of the site using a catheter tipped with iridium-192 radioisotope. In this method the iridium-192 tipped catheter is placed at the arterial site for thirty to forty minutes after stent deployment and then retracted. This type of acute high dose treatment using gamma radiation has been found to substantially reduce the rate of subsequent restenosis, as noted in Wiedermann, J. G. et al., "Intracoronary Irradiation Markedly Reduces Restenosis After Balloon Angioplasty in a Porcine Model," 23 J. Am. Coll. Cardiol., 1491-1498 (May 1994) and Teirstein, P. S. et al., "Catheter-Based Radiotherapy to Inhibit Restenosis After Coronary Stenting," 336 New England Journal of Medicine, 1697-1703 (Jun. 12, 1997).
An alternate method of addressing the restenosis problem is to embed within the structural material of the stent itself a radioactive material as described by Fischell R. et al. in U.S. Pat. No. 5,059,166 (the '166 patent) and in U.S. Pat. No. 5,376,617 (the '617 patent). The '166 and '617 patents also describe a method of electroplating a radioactive material on the structural material of the stent. Each of these methods has certain drawbacks. Placement of radioactive material within the structural material of the stent can present fabrication difficulties with respect to radiation exposure of workers during the manufacturing process. The electroplating process may result in poor adhesion of the radioactive material, which could delaminate during insertion. Because of the typically short half lives of the isotopes commonly used for medical treatments, both methods suffer from the difficulty of having to continuously maintain a stock of rapidly decaying active isotopes in order that the activity may be embedded as soon as possible before the medical procedure is performed. The radioactive stent thus fabricated has relatively short "shelf life".
Moreover, an additional requirement for any clinically useful stent is that it should have good x-ray visibility. A fairly thick (ten to fifteen micrometer) radiopaque coating of a high-density, high atomic number metal such as gold, platinum, iridium, or rhenium may be coated on the structural material of the stent in order to achieve visibility in an x-ray. The '166 and the '617 patents mention the possibility of plating the radioisotope Au.sup.198 on the structural material of the stent. Plating Au.sup.198 would not make the stent radiopaque because the coating would be less than a few Angstroms thick. As noted by Fishell et al. in the article "Low-Dose .beta.-Particle Emission From `Stent` Wire Results in Complete, Localized Inhibition of Smooth Muscle Cell Proliferation", 90 Circulation 2956-2963 (1994) (the Fischell article), radioactivity on the order of one microcurie is preferred for a coronary stent. Using an Au.sup.198 plating solution containing typically 18 Ci/g of dissolved gold (following a two-week cooldown period after activation in a nuclear reactor), a total activity of 1 .mu.Ci would require a total coating mass of 0.055 .mu.g, which, when distributed over the surface of an entire coronary stent, would have a thickness of about one atomic monolayer of gold. Such a thin layer would not add contrast in an x-ray picture of the stent. Moreover, Au.sup.198 is not a pure beta ray emitter. It also emits numerous gamma rays, which may provide an undesirable radioactive dose to the entire body of a patient instead of a localized dose to a target area in the coronary artery.
Another method mentioned in the Fischell article and further investigated by Laird, J. R. et al., in "Inhibition of Neointimal Proliferation with Low-Dose Irradiation from a .beta.-Particle-Emitting Stent," 93 Circulation 529 (Feb. 1, 1996) (the Laird article), is to impregnate titanium stents with up to thirty atomic percent of stable phosphorous and subsequently activate the entire stent in a nuclear reactor to form the radioisotope P.sup.31 within the titanium structural material. One of the disadvantages of the Laird method is that the massive quantity (30 atomic percent) of phosphorous required to make even 0.15 microcurie of P.sup.31 may severely alter the structural strength of the stent itself.
In the preferred embodiment of the '166 and '617 patents, the structural material in the body of the stent is alloyed with an activatable element and then subsequently activated in a nuclear reactor. When the body of a stent or any similar implantable medical device (including, without limitation, cancer irradiation needles, shunts, vascular grafts, bone screws, and femoral stem implants) contains significant quantities of iron and chromium, which is the case in stainless steel, for example, neutron activation produces long lived radioisotopes emitting a substantial quantity of gamma rays which generally would not be desirable for a permanent implant because of the high total body dose of radiation.
When the body of the medical device is fabricated from an alloy which includes the element nickel, the reactor activation produces significant quantities of the isotope nickel-63, which has a 100 year half life that is longer than the remaining lifetime of the human patient. Nickel is employed in shape-memory materials, such as NiTi, which is commonly known as nitinol. In nitinol, nickel is present with 50 atomic percent abundance. The radioactive decay of Ni-63 produces an undesirable background of low energy beta particles with an end point energy of 66.9 keV. While these beta particles have a relatively short range in tissue, approximately 0.08 mm, and may be partially absorbed within the nitinol, they are produced at a nearly constant rate for decades, and the total accumulated dose may, as a result, be undesirably high.